Achievement a Negative 18-FDG/PET Status at the End of Procedure by Tailored Treatment According Pre-Transplantation Pet Status in Lymphomas Improve 5 Years-OS and EFS.

In patients (pts) with non Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) with poor prognosis factors, pre-transplantation (ASCT) 18-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) status is important for evaluation of response and predicting the outcome. A positive pre-ASCT PET (+PET) indicated a high risk (HR) of relapse which was increased by a positive post-ASCT PET. For these patients additional therapy (salvage therapies prior ASCT, targeted radiotherapy, second transplant or new treatment approaches) will be required (Spaepen K 2001, Filmont JE 2003; Svoboda J 2006, Mounier, 2007). In a french regional network, we try to obtain a negative metabolic status with additive « targeted-therapy », before or after the ASCT, in the hope to improve the clinical outcome for these HR NHL/HD.

Objective: The study assessed the impact of tailored therapy according to pre-transplantation FDG-PET status on pts outcome after high-dose chemotherapy and ASCT.

Patients & Methods: We performed a retrospective analysis of pts included according three criteria: 1) histologically proven malignant lymphoma (NHL/HD) with a metabolic active disease in PET imaging 2) planned to receive an ASCT for HR factors according international recommendations (de novo initial aaIPI III/IV or not in CR after front line chemotherapy or in early and unfavorable relapse; 3) having a PET prospectively performed prior and after ASCT on a CDET replaced in 2005 by a PET/CT (Siemens). The metabolic imaging interpretation had been performed by 2 experienced nuclear physicans first blinded to clinical and CT scan then discussed in multidisciplinary team. + PET defined as any focal or diffuse area of increased activity in a location suspect for residual disease and -PET if any metabolic activity according revised Cheson criteria. Survival analysis were performed using Kaplan-Meier method for event free survival (EFS), overall survival (OS).

Results: For 95 consecutive pts treated from 05/1999 to 12/2006 18 HD and 77 NHL, an ASCT has been planned either in initial HR prognostic score (n=39), primary refractory disease (n=31), or in relapse (n=25). First line therapy were mainly ABVD for HD and ACVBP/CHOP +/− Rituximab for NHL. A pre-ASCT -PET was obtained in 52 pts (55%) and 43 pts (45%) remained pre-ASCT +PET. Additional salvage chemotherapy (MINE or DHAP(+/−R) most frequently) obtained a - PET status from pre-ASCT +PET in 9/43 pts (21%) prior the ASCT. ASCT has been performed for all these HR pts with a conditioning regimen mainly BICNU-Etoposide-Aracytine-Melphalan (BEAM). After ASCT, 22/43 pre-ASCT +PET pts were converted in a post-ASCT -PET status. Residual disease of post-ASCT +PET pts was treated by targeted radiation (n=11) or by a second transplant (n=2). One pre-ASCT -PET converted to positive (1/52). At the end of procedure, we obtained a –PET status in 88 pts (92%), persistant + PET in 7 pts (7%) (3 PR/4 PD). With a median follow-up of 4.14 years (range 0.61–9.48) since diagnosis, 15/43pts (35%) pre-ASCT +PET and 14/52pts (26%) pre-HDT/ASCT -PET pts relapsed. Mortality was 23% (22/95pts range -PET : 11/52 (21%) and +/−PET 11/43 (25%) respectively and 4/7 (57%) resistant +/+PET). In –PET and in +/−PET median OS and EFS were not reached, 5yOS was 79% and 73% (p=0.7) and 5 y-EFS 62% and 54% respectively (p=0.2). In residual post-ASCT+PET, median OS was 4,5 months.

Conclusion: PET-guided consolidative therapy prior or post ASCT in patients with HR lymphoma is routinely feasible and could obtain a negative status in 92% of pts at the end of procedure and reduce relapses with encouraging results in terms of OS and EFS with a 5-y median follow-up. Next step is now on-going: including pts in multicentric PETdesigned trials to confirm prospectively the crucial role of the metabolic imaging to determine which is the best tailoring therapy.